Perry disease: recent advances and perspectives

ABSTRACT

Introduction: Perry disease, which is also widely known as Perry syndrome, is a rare autosomal dominant neurodegenerative disease clinically characterized by parkinsonism, depression/apathy, weight loss, and respiratory symptoms. Perry disease is pathologically classified as a TAR DNA-binding protein 43 (TDP-43) proteinopathy. In addition to the presence of mutations in the causative gene for the disease, DCTN1, Perry disease patients show relatively uniform clinical and pathological features. Thus, recently the nomenclature of ‘Perry disease’ has been proposed as being more appropriate than ‘Perry syndrome.’

Areas covered: This review summarizes recent findings of Perry disease from the perspective of both clinical and basic science. Furthermore, future challenges and prospects for the treatment for Perry disease are discussed.

Expert opinion: Among various clinical features, respiratory insufficiency including central hypoventilation is the most devastating symptom in patients with Perry disease. A diaphragmatic pacemaker may be an option for respiratory insufficiency. The development of disease-modifying therapies for Perry disease requires basic science studies and clinical trials, along with the study of other neurodegenerative diseases.

KEYWORDS:

• Perry disease
• Perry syndrome
• DCTN1
• dynactin
• TDP-43

Article highlights

• Perry disease is a rare autosomal dominant neurodegenerative disease clinically characterized by parkinsonism, depression/apathy, weight loss, and respiratory symptoms.

• Perry disease is pathologically classified as a TAR DNA-binding protein 43 proteinopathy.

• DCTN1 mutations are reported in all patients with Perry disease. The DCTN1 gene encodes p150^Glued, the large subunit of the dynactin complex.

• Clinician should use the diagnostic criteria of Perry disease for early diagnosis.

• Perry disease has overlapping clinical features, genetics, and pathology with other neurodegenerative diseases.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by JSPS KAKENHI (TM, 18K15471) and Research on Rare and Intractable Diseases, Health and Labour Sciences Research Grants.